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Comprehensive study of transcriptional control processes will be required to enhance our understanding of both normal and malignant hematopoiesis. Modern sequencing technologies have revolutionized our ability to generate genome-scale expression and histone modification profiles, transcription factor (TF)-binding maps, and also comprehensive chromatin-looping information. Many of these technologies, however, require large numbers of cells, and therefore cannot be applied to rare hematopoietic stem/progenitor cell (HSPC) populations. The stem cell factor-dependent multipotent progenitor cell line HPC-7 represents a well-recognized cell line model for HSPCs. Here we report genome-wide maps for 17 TFs, 3 histone modifications, DNase I hypersensitive sites, and high-resolution promoter-enhancer interactomes in HPC-7 cells. Integrated analysis of these complementary data sets revealed TF occupancy patterns of genomic regions involved in promoter-anchored loops. Moreover, preferential associations between pairs of TFs bound at either ends of chromatin loops led to the identification of 4 previously unrecognized protein-protein interactions between key blood stem cell regulators. All HPC-7 data sets are freely available both through standard repositories and a user-friendly Web interface. Together with previously generated genome-wide data sets, this study integrates HPC-7 data into a genomic resource on par with ENCODE tier 1 cell lines and, importantly, is the only current model with comprehensive genome-scale data that is relevant to HSPC biology.

Original publication

DOI

10.1182/blood-2015-10-677393

Type

Journal article

Journal

Blood

Publication Date

31/03/2016

Volume

127

Pages

e12 - e23

Keywords

Animals, Binding Sites, Cells, Cultured, Chromatin Immunoprecipitation, Embryo, Mammalian, Gene Expression Regulation, Genome, HEK293 Cells, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mice, Mice, Transgenic, Promoter Regions, Genetic, Protein Binding, Regulatory Sequences, Nucleic Acid, Transcription Factors